The breakthrough approach is commonly used, but the devil is in the details.

Determining and Optimizing Dynamic Binding Capacity

In this article, a simple chromatographic model is proposed that is capable of predicting the impact of pH and ionic strength on HIC chromatograms.

Purification of Protein by HIC: Mechanistic Modeling for Improved Understanding and Optimization

The COVID-19 vaccines opened the door to powerful market potential for other nucleic acid-based therapies.

Ramping Up Development of Nucleic Acid Therapies

The innovation of going from stainless-steel bioreactors to fixed-bed bioreactors shows an evolution in upstream optimization.

Exploring the Impact of Fixed-Bed Bioreactors in Upstream Processing

Makers of specialty biologics, gene therapies, and other personalized medicines are working to identify and reduce potential supply chain risks both upstream and downstream.

Reducing Vulnerabilities in Upstream and Downstream Supply Chains

FDA has spurred investment to create and develop 600 therapies.

Kudos and Hurdles in Tackling Rare Diseases

What can we take away from Pfizer's acquisition of Seagen?

 Zauberkugel: Pfizer’s Seagen Acquisition

Astellas Pharma announced on May 25, 2023 that Astellas B.V., Astellas Pharma Europe B.V., and Astellas’ subsidiaries in the Netherlands have decided to sell and transfer the manufacturing plant located in Meppel to Delpharm Industries. This agreement is intended to be executed and see the impact of any financial transfers by the fiscal year ending March 31, 2024.

Astellas hopes to continue to strengthen its capabilities in the technology and manufacturing sector, and it hopes to partner with Delpharm for promoting a more stable supply of high-quality medicines, according to the company press release. Under the agreement, Delpharm will continue to manufacture the products that are currently manufactured at the Meppel plant, with these products being delivered to the Astellas group. Further, employees from Astellas will also transfer to Delpharm.

Articles

This agreement is intended to be executed and see the impact of any financial transfers by the fiscal year ending March 31, 2024.

Astellas Pharma to Transfer Manufacturing Plant, Business to Delpharm 

Feliza Mirasol is the science editor for 

FDA announced on May 19, 2023 that it granted approval to Krystal Biotech, a US-based biotechnology company focused on genetic medicines for rare diseases, for the company’s product, Vyjuvek (beremagene geperpavec-svdt), a herpes-simplex virus type 1 (HSV-1) vector-based gene therapy. The indication is for treating wounds in patients six months of age and older who have dystrophic epidermolysis bullosa (DEB) with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene. According to an agency press release, Vyjuvek is the first topical gene therapy approved for this indication.

DEB is a genetic disorder affecting the connective tissue in the skin and nails. It is caused by mutation(s) in the COL7A1 gene, which encodes type VII collagen (COL7), an essential protein that helps strengthen and stabilize the outer and middle layers of the skin, according to the agency’s press release. A COL7A1 deficiency leads to separation of skin layers, which causes painful and debilitating blisters and wounds. The disorder usually shows at birth and is divided into two major types depending on the inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB).

Symptoms can vary. Individuals with DDEB typically experience mild cases; blistering primarily affects the hands, feet, knees, and elbows. In comparison, RDEB cases can be painful and debilitating, and often involves widespread blistering that can lead to vision loss, disfigurement, and other serious medical complications that can be fatal, according to the FDA press release.

Vyjuvek is a genetically modified herpes-simplex virus that is used to deliver normal copies of the COL7A1 gene to the wounds, which then helps to hold the layers of skin together, maintaining the integrity of the skin. The FDA release reports that Vyjuvek has also been modified such that it cannot replicate in normal cells. According to clinical study results, 65% of Vyjuvek-treated wounds completely closed compared to only 26% complete-wound-closure in placebo-treated subjects.

“Vyjuvek is the first FDA-approved gene therapy treatment for DEB, a rare and serious genetic skin disorder,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, in the release. “Today’s action demonstrates [FDA]’s ongoing commitment to supporting the development and evaluation of new treatments that address unmet needs for rare diseases or conditions.”

FDA has approved the first topical gene therapy product for treating wounds in patients with dystrophic epidermolysis bullosa.

FDA Approves Topical Gene Therapy for Treating Wounds Associated with Rare Genetic Skin Disorder

AbbVie announced on May 19, 2023 that FDA has approved EPKINLY (epcoritamab-bysp), a T-cell engaging bispecific antibody for treating relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The bispecific is particularly indicated for treating adult patients with R/R DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma and high-grade B–cell lymphoma (HGBL). Administration of the bispecific is intended for patients who have already had two or more lines of systemic therapies.

According to a company press release, DLBCL patients are typically treated with chemoimmunotherapy-based regimens, but several targeted therapies, including T-cell mediated treatments, have recently emerged for R/R patients. A single agent and ready-available or off-the-shelf treatment options, however, remain limited.

"DLBCL is an aggressive cancer type that can rapidly progress and resist treatment. The FDA approval of EPKINLY represents a new treatment mechanism of action for third-line DLBCL patients,” said Thomas Hudson, senior vice-president, research and development, chief scientific officer, AbbVie, in the press release. “As a non-chemotherapy, single-agent treatment for DLBCL patients, we hope that [epcoritamab-bysp] can effectively treat this aggressive cancer type and can be used for patient care quickly and in an off the shelf form for physicians."

"Patients with DLBCL who relapse or are refractory to currently available therapies have limited options. Generally, the prognosis for these patients is poor and management of this aggressive disease can be challenging," said Tycel Phillips, City of Hope associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, in the release. "Epcoritamab is a subcutaneous bispecific antibody that offers an additional treatment option for this patient population. With this approval, patients who are in need of additional therapy may have the opportunity to receive epcoritamab after failure to respond or relapse after two or more systemic therapies."

AbbVie co-developed epcoritamab-bysp with partner Genmab as part of an oncology collaboration between the companies.

FDA has approved AbbVie’s EPKINLY (epcoritamab-bysp), a bispecific antibody for treating relapsed or refractory diffuse large B-cell lymphoma.

FDA Approves AbbVie’s Bispecific Antibody for Treating Lymphoma

Editor of Pharmaceutical Technology Europe

 podcast, Felicity Thomas, European/Senior Editor, talks to Hanns-Christian Mahler, CEO and board member, and Andrea Allmendinger, chief scientific officer, both at ten23 health—a contract development and manufacturing organization dedicated to human-centric and sustainable pharmaceutical development—about some of the hurdles facing developers and manufacturers of biological therapies. Hanns-Christian and Andrea take a closer look at some of the solutions being used within industry to overcome these challenges and focus on the issue of sustainability within this sphere. Finally, they touch upon some of the other potentially important future trends that will impact biologic drug development and manufacturing.

Hanns-Christian Mahler is Chief Enablement Officer (CEO) & Board Member, ten23 health

. Mahler’s previous roles include the head of Drug Product Services at Lonza, head of Pharmaceutical Development and Supplies at Roche, and principal scientist of Pharmaceutical Development and CMC Project Manager Erbitux for Merck KGaA. He holds a PhD in Toxicology from the Institute of Pharmacy at the University of Mainz and is an adjunct faculty member and lecturer at the universities of Frankfurt and Basel. He obtained his venia legendi (German Habilitation) from the University of Frankfurt/M. in 2011. Mahler also serves on the boards of Bionter and KriyaBio, and is an editor for several pharmaceutical journals.

Andrea Allmendinger, PhD, Chief Scientific Officer at ten23 health.

 Dr Allmendinger is also Adjunct Professor and Group Leader at the University of Freiburg (Baden-Württemberg, Germany), researching novel parenteral drug formulations and device solutions to improve stability, usability and cost of goods. Between 2010 and 2021, she was Principal Scientist, Pharmaceutical Development at Roche, working on, inter alia, manufacturability and injectability of high-concentration protein formulations, formulation and process development of freeze dried formulations, syringe and high volume drug/device combination products, particulates and surfactant strategy. Dr Allmendinger studied Pharmacy at the University of Heidelberg, Germany, and University College London, UK, and holds a PhD in Pharmaceutical Sciences from the University of Basel, Switzerland. She obtained the venia legendi (German Habilitation) from the University of Freiburg in 2021, and serves as Editor-In-Chief for the AAPS Open Journal.

Podcasts

Hanns-Christian Mahler and Andrea Allmendinger from ten23 health will discuss some key aspects of biologic drug development and manufacturing.

Drug Solutions Podcast: Considering Biologic Drug Development and Manufacturing Holistically

TriLink BioTechnologies announced the expansion of its messenger RNA (mRNA) manufacturing capabilities on May 24, 2023. The new construction of the current good manufacturing practice (CGMP)-grade facility will help the company with its mission to advance the field as more mRNA-based therapeutics and vaccines enter later-stage clinical trials, according to the company press release.

Further, the new CGMP facility is expected to contribute to the development of mRNA therapeutics, with a building designed for the CGMP manufacture of mRNA-based 

 gene editing, gene-edited cell therapies, protein replacement therapies, cancer vaccines, and infectious disease vaccines.

“The expansion of our CGMP mRNA manufacturing capabilities marks a major milestone for TriLink and our partners,” said Becky Buzzeo, chief commercial officer at Maravai LifeSciences, in a press release. “Drug developers will soon be able to leverage our team’s 25-plus years of industry expertise, helping to take critical therapeutics from concept to plasmid DNA through to late-phase clinical mRNA drug substance manufacturing with ease.”

The facility will include ISO 7 cleanrooms and increased mRNA capacity, which will also feature comprehensive in-house analytical services, according to the press release.

“Our team took great care in building and designing our new facility– it’s truly been a labor of love,” added Rob Carpenter, vice president of Engineering at TriLink, in a press release. “In addition to having access to a state-of-the-art facility, developers will also have a direct line to our experienced team to help with process optimization, scale-up, validation, and qualification capabilities.”

The new CGMP facility is expected to contribute to the development of mRNA therapeutics, with a building designed for the CGMP manufacture of mRNA-based in-vivo gene editing, gene-edited cell therapies, protein replacement therapies, cancer vaccines, and infectious disease vaccines.

TriLink BioTechnologies to Expand Manufacturing Capabilities 

Aurigene Pharmaceutical Services, a contract research, development, and manufacturing organization (CDMO), announced on May 22, 2023 the construction of a state-of-the-art development and manufacturing facility for therapeutic proteins, antibodies, and viral vectors.

The first steps show Aurigene investing $40 million in an R&D and pilot-scale facility at Genome Valley, which is set to meet the process development and clinical supply needs of global biotech companies, according to a company press release. Further, the facility is based on a state-of-the-art design concept that allows maximum flexibility for a multi-product, multi-platform offering.

Set to be fully operational by 2024, the facility hopes to continue to be a strong presence in the biotherapeutics space, as it is complemented by exclusive access to an established large-scale good manufacturing practice (GMP) manufacturing facility with a drug substance capacity of 15kl and fill/finish capabilities. Additionally, another fill/finish line is under construction to be validated before the end of 2024, according to the press release.

“We see an increased outsourcing demand from global biopharmaceutical companies. With this expansion in biotherapeutics CDMO, we will be positioned to provide integrated services from clinical research to commercial manufacturing for small and large molecules,” said Akhil Ravi, CEO of Aurigene Pharmaceutical Services Ltd., in a press release. “Investing in emerging technologies and health solutions reinforces our aim to triple our existing reach to touch over 1.5 billion patients worldwide by 2030.”

The facility is based on a state-of-the-art design concept that allows maximum flexibility for a multi-product, multi-platform offering.

Aurigene Pharmaceutical Services Expands with New Facility 

Drug development is inherently costly and time-intensive, with potential attrition serving as a persistent burden on bio/pharma companies’ finances (1). As companies gain a deeper understanding of cell and molecular biology and seek to develop more complex therapeutics for patient populations, they will also need to be more innovative to ensure commercially viable success is achieved (2).

An area that has witnessed significant breakthroughs over recent years has been that of cell and gene therapies. The market for these emerging therapies is projected to grow at a compound annual rate of 22.41% between 2022 and 2030 (3), driven by an expanding pipeline and increasing regulatory approvals.

Despite the successes that have already been achieved with emerging therapy development and manufacturing, companies are still facing numerous challenges. Aspects such as demand for accelerated development timelines, advancing technologies, and the growing issue surrounding sustainability are monopolizing the priorities of bio/pharma companies. However, through new opportunities, such as allogeneic cell therapy, it is hoped that greater benefits to patients, particularly those in undertreated populations, will be achieved (4).

In speaking with Øystein Åmellem, director of Cell Therapy at Thermo Fisher Scientific, and Evan Zynda, senior staff scientist at Thermo Fisher Scientific, 

® discussed with them how standardization is the future for emerging therapies, and tackling challenges such as scalability will get the industry to that point.

Continued investment in cell and gene therapies

 Is there anything specific you are seeing in terms of new emerging therapy development or manufacturing in the industry as of now?

Åmellem/Zynda (Thermo Fisher Scientific):

 One of the biggest manufacturing trends we are currently seeing is a growing focus on standardization. The current lack of standardization within the industry can be attributed to the recent rapid growth of the cell therapy market and the associated drive to improve the efficiency and cost-effectiveness of production. This has led many companies to develop their own unique manufacturing workflows.

Although this has been beneficial on an individual basis, increased standardization has the potential to improve manufacturing across the industry. For example, it can help simplify processes and reduce production costs in the long term. Additionally, standardized approaches, particularly those that incorporate automation and utilize closed systems, can reduce the risk of manufacturing failures or contamination—helping manufacturers to consistently deliver safe and efficacious therapies.

Addressing new short- and long-term challenges

 Are there any new challenges or hurdles in the cell therapy space that should be addressed for the short- and long-term?

 A key challenge that must be addressed is scalability. For developers working in the allogeneic space, there is a need to scale up production to meet the projected future demand for these therapies while also keeping manufacturing workflows closed. Conversely, in the autologous space, there is a focus on scaling down production to rapidly produce smaller doses and prioritize optimal cell quality. In terms of addressing these needs, innovative manufacturing solutions are essential. For instance, standardized, closed-system equipment that can be flexibly used to scale production of both types of therapies, without compromising on either safety or cost-effectiveness, can have a hugely positive impact.

The benefits of utilizing allogeneic cell therapies

 Why are companies starting to look at allogeneic cell therapies more closely?

 In addition to their ability to improve time-to-treatment and treatment efficacy, allogeneic cell therapies have several strategic advantages for biopharmaceutical manufacturers. Most notably, batch sizes of allogeneic therapies are generally much larger, with the intention of freezing down several doses. This can offer considerable benefits by reducing both the production cost per dose and, in turn, the treatment cost for patients.

Industry players and allogeneic therapies

 Are allogeneic cell therapies a bigger opportunity for industry players, such as contract development and manufacturing organizations (CDMOs) and contract research organizations (CROs), and why?

 There are several reasons why allogeneic therapies are seen as an opportunity for both CROs and CDMOs. For example, the rapid growth of this therapeutic area has led to skills and knowledge gaps within the industry, particularly around regulatory requirements, which can be filled by working with an experienced partner. Additionally, the scaled-up production volumes employed for allogeneic therapies mean that maximizing manufacturing capacity is an essential consideration; however, building this capacity in-house can be both financially and logistically challenging. Thus, choosing to outsource production to a CDMO can be the most effective choice, especially for smaller companies.

 What do you hope to see for the future of allogeneic cell therapies/any other emerging therapy development or manufacturing?

 Further advancements in cell culture media could be highly beneficial. For example, optimizing media for different manufacturing workflow stages could lead to an improved therapeutic product. From a logistical point of view, increased digitalization of documentation such as batch records could help to dramatically simplify workflows and reduce manual workloads, lowering manufacturing costs. This would have the additional benefit of improving overall process control, which is key for optimizing consistency during large-scale cell therapy production.

 Beyond cell therapies and gene therapies, what other categories of emerging therapies are being developed, and can we expect to see approvals for those in the near future?

 One of the biggest future opportunities within the cell therapy field is utilizing other immune cells beyond T cells as a therapeutic product. Natural killer cells have attracted considerable attention as they are seen as a more feasible option for producing allogeneic therapies. There is also a growing interest in using cell-based immunotherapies to treat solid tumors. Although there are still several challenges, including overcoming the radically different tumor microenvironment, clinical success within this area has the potential to lead to a major shift in cancer treatment.

Agrawal, G.; Keane H.; Prabhakaran, M.; Steinmann, M. The Pursuit of Excellence in New-Drug Development. McKinsey & Company, Nov. 1, 2019. 

https://www.mckinsey.com/industries/life-sciences/our-insights/the-pursuit-of-excellence-in-new-drug-development

McKinsey & Company. How AI Can Accelerate R&D for Cell and Gene Therapies. 

https://www.mckinsey.com/industries/life-sciences/our-insights/how-ai-can-accelerate-r-and-d-for-cell-and-gene-therapies

Cell and Gene Therapy Market (by Therapy Type: Cell Therapy and Gene Therapy; by Indication: Cardiovascular Disease, Cancer, Genetic Disorders, Infectious Diseases, Neurological Disorders; by Delivery Method: 

; by End-Users: Hospitals, Cancer Care Centers, Wound Care Centers, Others)—Global Industry Analysis, Size, Share, Growth, Trends, Regional Outlook, and Forecast 2022–2030

Fontanillo, M.; Paulick, K.; Poda, P.; Silberzahn, T. Out of the Shadows: A Brighter Future for Pharma Technical Development. McKinsey & Company, Sept. 16, 2022. 

https://www.mckinsey.com/industries/life-sciences/our-insights/out-of-the-shadows-a-brighter-future-for-pharma-technical-development

The current lack of standardization within the industry can be attributed to the recent rapid growth of the cell therapy market and the associated drive to improve the efficiency and cost-effectiveness of production. 

Expanding the Emerging Therapeutic Horizon through Standardization

Mustang Bio, a US-based clinical-stage biopharmaceutical company, announced on May 18, 2023 that it has entered into an agreement with uBriGene Biosciences, the US subsidiary of uBriGene Group, a China-based cell and gene therapy (CGT) contract development and manufacturing organization (CDMO). According to the terms, uBriGene will acquire Mustang Bio’s commercial-scale CGT development, manufacturing, and analytical testing facility in Worcester, Mass.

Under the agreement, uBriGene will acquire the Worcester facility for a total consideration of $11 million, which includes a $6 million upfront payment plus an additional $5 million payable upon Mustang raising $10 million in equity after the close of transaction. The transaction is expected to close in June 2023 dependent on closing conditions.

Also under the agreement, and subject to closing, uBriGene and Mustang will enter into a manufacturing supply agreement, under which uBriGene will manufacture Mustang’s lead product candidates. According to a uBriGene company press release, uBriGene will also take over the clinical manufacturing of MB-106, Mustang’s chimeric antigen receptor T cell (CAR-T cell) therapy for treating a wide range of hematologic malignancies, including Waldenstrom macroglobulinemia, a rare malignant disorder of the bone marrow and lymphatic tissues. According to a Mustang company press release, uBriGene will continue to support MB-106 manufacturing for the duration of an ongoing multi-center Phase I/II trial.

 current good manufacturing practice-compliant facility that supports process development, manufacturing, and analytical testing of CGTs. It is designed to be flexible and to expand and support various CGT production requirements and capacities. uBriGene intends to expand the site’s capabilities to manufacture a broader portfolio of advanced modalities with the help of Mustang’s experienced staff and robust quality and operating systems. According to Mustang’s company press release, uBriGene will also offer its expertise in preclinical research services and late-stage and commercial manufacturing of advanced therapy products; in particular, uBriGene will bring to bear its expertise in product and process characterization as well as regulatory inspections.

“We are very pleased to have found a great partner for the manufacturing of our CAR-T cell and gene therapies, and we believe that this strategic partnership with uBriGene will meet our portfolio manufacturing needs to reach critical upcoming data inflection points, while extending our cash runway. I want to thank our manufacturing team for their dedication in building and growing our Worcester facility since it opened in 2018. While we are optimizing our resources at Mustang, we look forward to continuing to work with many of our colleagues in this new capacity, as our CDMO,” said Manuel Litchman, president and CEO of Mustang, in that company’s press release.

“This acquisition is important to uBriGene’s commitment to support the development, clinical, and commercial supply of cell and gene therapies to sustain industry demand and provide new CDMO options,” said Alex Chen, president of uBriGene, also in the Mustang release. “We look forward to working together with the University of Massachusetts Chan Medical School and local biotechnology companies to continue to advance the manufacturing ecosystem in the Greater Boston region. This partnership enables us to expand rapidly to create a North American presence and offer the same high-quality cell and gene therapy development and manufacturing capabilities for the U[nited] S[tates] that we currently provide in Asia, including to support Mustang Bio’s lead clinical-stage CAR-T program.”

uBriGene Biosciences will acquire Mustang Bio’s Worcester, Mass., CGT manufacturing facility in a deal worth up to $11 million, expanding its operations into the US market.

uBriGene Expands into US Market with Acquisition of Mustang Bio's CGT Manufacturing Facility

Myeloid Therapeutics, a US-based clinical-stage messenger RNA (mRNA)-immunotherapy company, announced on May 18, 2023 that investment firm Hatteras Investment Partners has completed a round of financing totaling $73 million, which included participation from new investors, ARCH Venture Partners and Moore Strategic Ventures, as well as existing investors, Newpath Partners, 8VC, and Alexandria Venture Investments.

According to a company press release, proceeds from the financing will support Myeloid’s continued clinical development of MT-101, its lead cell therapy program in Phase I/II studies for T-cell lymphoma. The funding will also accelerate the development of MT-302, a trophoblast cell-surface antigen 2 (TROP2)-FcA mRNA-lipid nanoparticle (LNP) product, into a Phase I/II study for TROP2-expressing tumors. The funding will also help advance additional 

“Myeloid continues to make significant progress across all aspects of our business. We are pioneering the convergence of immunology and RNA science to build a clinical-stage portfolio of products, starting with the significant unmet needs of cancer patients,” said Daniel Getts, CEO of Myeloid, in the press release. “We are pleased that such high-quality investors have joined with us to accelerate this effort.”

“We are highly encouraged by the innovation, execution, and clinical development progress demonstrated by Myeloid. We are proud to support this [company] through its next phase of growth and are optimistic that these approaches will drive a meaningful clinical outcome for patients,” said Clay B. Thorp, general partner at Hatteras, in the release.

With $73 million in financing from investment firms, Myeloid Therapeutics plans to accelerate its lead clinical candidate into Phase I/II development for treating solid tumors.

Myeloid Therapeutics Gets $73 Million to Advance mRNA-based Pipeline

Revvity, Inc. announced on May 18, 2023, a new license agreement with AstraZeneca for the technology underlying technology in its Pin-point base editing system, which is a next-generation modular gene editing platform with a strong safety profile.

The Pin-point system and the base editing technology is defined as allowing highly efficient, precise single and multi-gene editing without unintended impact on cell viability or functionality. According to the press release, this newer editing system uses a modified Cas enzyme that only marks one strand of the DNA, which allows for a more controlled approach to gene distribution and base correction.

Different from other editing systems, the pin-point system is completely modular, allowing for different components to be selected for optimal performance specific to the gene targets. Additionally, Revvity has also developed a novel proprietary method to leverage the base editing mechanism to insert genes, like creating an allogeneic CAR-T cell therapy by knocking in a CAR while knocking out immune markers at the same time, according to the press release.

“Our fundamental goal for the Pin-point platform is to translate the technology from pre-clinical research into the clinic, and ultimately, impact patient lives,” said Alan Fletcher, PhD, senior vice president, Life Sciences at Revvity, in a press release. “In that vein, we are delighted to announce this non-exclusive agreement with AstraZeneca to support their creation of cell therapies for the treatment of cancer and immune-mediated diseases.”

The pin-point system is completely modular, allowing for different components to be selected for optimal performance specific to the gene targets.

New License Agreement Announced for Next-Generation Base Editing Technology 

Grant Playter is the Assistant Editor for 

While the world may have marched on from the halcyon days of the mid-20th century where the United States was the undisputed center of the global economy, the country’s continual impact should not be understated. Particularly as it concerns the biopharmaceutical industry, the US remains a powerful influencer; not only has it proved to be fertile ground for the growth of pharmaceutical powerhouses such as Pfizer and Johnson & Johnson, the country’s 330+ million population is a substantial target for overseas pharmaceutical companies.

That is not to say that powerful players, including the likes of China, Japan, and the European Union (EU) member countries are of lesser importance. Rather, it stresses the reality that the US, for the foreseeable future, is the largest pharmaceutical market; Fortune Business Insights valued the US at a world-leading $534 billion in 2020 and anticipated strong growth to $861 billion by 2028 (1). Correspondingly, a comprehensive understanding of the global biopharmaceutical market is contingent on thorough knowledge of the US landscape and ongoing events in the country. In this vein, while the ink has long dried on the Inflation Reduction Act, the bill must be examined with close scrutiny to understand its full impact on the global bio/pharmaceutical market.

Following narrow votes in both chambers of the US Congress, President Joe Biden signed The Inflation Reduction Act of 2022 (IRA) into law on Aug. 14, 2022 (2). While the $740 billion bill was a compromise among senate Democrats following failure to reach a consensus on a proposed $2.2 trillion framework (colloquially referred to as the “Build Back Better” bill), which aimed to have a transformative “cradle to casket” impact on American healthcare, IRA is nonetheless set to have a discrete impact on the healthcare throughout the country.

While the bill does not solely focus on healthcare, it introduces several key reforms that are set to introduce price controls on medicines. The bill will limit out-of-pocket costs for Medicare beneficiaries at $2000 a year beginning in 2025, passing additional costs onto drug manufacturers. Additionally, starting in 2026, the US government will also be able negotiate Medicare prices on 10 widely-used, costly medicines; this number will be expanded to 20 in 2029. If this price is rejected by the manufacturer, they will be charged a significant fee (3).

One aspect of the bill that has raised a few eyebrows is the difference in the negotiation window between small molecules and biologics; small molecules sit at nine years following FDA approval, whereas biologics are 13 years (4). This variation has led to many outspoken critics of the bill, including John Stanford, executive director of the Incubate Coalition. Incubate is an organization representing various venture capital organizations that seeks to “educate policymakers on the role of venture in bringing promising ideas to patients in need” (5).

“The bill shows a misunderstanding of the basic science—we shouldn’t be incentivizing biologics or small molecules,” says Stanford. “If the cure for Alzheimer’s is a biologic infusion, great. If it’s a small molecule, that’s great too. But now, from an investment perspective, I’m more interested in 13 years than nine years, and that’s a big flaw that’s going to have pretty damning consequences over the next couple of decades.”

According to Stanford, the discrepancy may have arisen from an existing misconception that small molecules were already disadvantaged from an investment perspective. The existing framework for exclusivities is five years for small molecules and twelve years for biologics, but this understanding does not factor additional factors, such as the role of the 20-year patent and possible add-ons.

However, while most agree that some amount of innovation will be lost as profit margins slim and investment risk increases, there is little consensus as to what that will look like. For instance, the US Congressional Budget Office estimated that the drug negotiation provision would ultimately result in a 1% decline in new drugs being introduced to the US market over the next 30 years (6). Others, such as Stanford, feel strongly that this will have broader consequences.

“Capital flows like water. I don't think tomorrow life sciences funds are going to dry up. But there's more barriers, more risk, now going to be associated with it,” says Stanford. ““We have dramatically decreased the perceived reward while increasing the risk.”

Stanford’s argument is that companies will look to diversify and mitigate risk. If $100 million in investment capital would have completed seed funding for 10 life science companies in the past, after these changes, that amount might only fund five life sciences companies as investors look to segments such as banking or technology for alternative investment opportunities. The inherent complexity of the biopharmaceutical development process already makes it a risky bet for venture capitalists; increasing the burden placed on them has a strong possibility of decreasing investor interest in innovations that would otherwise be seen as interesting.

In a similar vein, one could argue that there are already potential knock-on effects from the bill impacting the industry. For instance, the IRA attempted to codify a $35 price cap on insulin for recipients with Medicare and private healthcare coverage. However, because regulating private insurers fell outside the purview of reconciliation (a legislative process that allows for certain bills to pass with a simple majority of votes) that portion of the provision was put to a vote and axed from the bill (7). However, the provision remained intact for Medicare recipients, and arguably set a precedent for Eli Lilly and Company’s decision to cap their insulin prices in the United States at that price in March 2023 (8). Regardless of whether one believes Lilly would have set the cap independent of the bill, it remains prudent for industry experts to acknowledge its potential downstream impacts on bio/pharmaceutical businesses.

Of course, the US doesn’t operate in a vacuum—it’s just one part of the greater global biopharmaceutical market. A market which, as discussed in the 2022 CPHI annual market report, has effectively bottomed out in terms of investment, with hundreds of billions sitting in parked capital (9). Investment, however, is cyclical, and the authors of the report acknowledged that this money will likely have to enter the industry at some point within the next 18 to 24 months. In this regard, of note are the findings of 

s annual survey where approximately half of industry respondents felt that cell and gene therapies presented the biggest avenue for growth (10). However, if the IRA does have a negative impact on investment in US biologics, it begs the question: where will this money go?

“If the US has been degrading its investment appetite through policy, threats to intellectual property, and price controls, China has been going the other way,” says Stanford. “China has extended intellectual property. China is trying to make a warm investment environment.”

China’s rapid economic growth has been the story of the 21st century, and the biotechnology market is no different. The Chinese biotechnology market had total revenues of $23.2 billion in 2020, representing a compound annual growth rate (CAGR) of 8.5% between 2016 and 2020 (11). If the disincentive is strong enough for investors to take pause, it’s entirely possible that looser regulations and the potential for greater profits could bring them to China.

Another contender is Europe, which, as of 2021, had a pharmaceutical market valuation of $282.75 billion (12). Stanford suggested that if the EU were to relax various price controls, à la China’s recent efforts or the US’ implementation of measures such as the Bayh-Dole Act in the 1980’s (13), the EU could easily pick up many of the investment dollars being left on the table in the US.

However, where the capital ultimately ends up is largely moot in terms of US interests: while the government would certainly prefer these dollars go to strongly aligned countries, any investment outside of the US is obviously not preferred. Congress has aggressively pursued bipartisan measures at keeping industry in America; the Creating Helpful Incentives to Produce Semiconductors (CHIPS) and Science Act (14), which aimed to take semiconductor business from countries such as China, was passed shortly before the IRA. If the bio/pharmaceutical provisions in the IRA move an equal or greater amount of investment out of the US, then Congress’ efforts at keeping industry housed within the US would be hampered.

The question regarding the IRA isn’t necessarily what will happen regarding investment funding, but, rather, how big of the pie will be leaving the country, and where is it going? No one, including Stanford and his contemporaries, is expecting a mass exodus of biotech funding from the US. If the Congressional Budget Office’s number sticks, most businesses wouldn’t bat an eye. If the impact is more in line with the expectations of Stanford and company, it could severely stifle market growth.

Unfortunately, while it would be courteous of investors to kindly explain why they chose one option over another in detail, oftentimes the downstream effects of decisions such as this are hard to isolate—investors themselves might not fully appreciate the various confounding factors that led them to a decision. However, as competition continues to build in the global bio/pharmaceutical market, tracking where biotech investments in totality are occuring could perhaps give at least a glimpse into the answer.

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Context surrounding the Inflation Reduction Act is necessary for a comprehensive understanding of the global biopharma market.

The United States and the Global BioPharma Market

Chris Spivey is the editorial director of 

Chris Spivey, editorial director, speaks with Jane True, vice-president of mRNA Commercial Strategy & Innovation and Global Pandemic Security Lead, Pfizer. In this interview, True shares her perspective on how mRNA will shift commercial models in the pharmaceutical industry, including changes to the "just-in-time" supply chain, pandemic preparedness, and more.

Jane True, vice-president of mRNA Commercial Strategy & Innovation and Global Pandemic Security Lead, Pfizer, shares her perspective on how mRNA will shift commercial models in the pharmaceutical industry.